Disease/Drug of Interest: Poliomyelitis is prevented by vaccination and is treatment with an assortment of medicines if contracted. Motivation and Background: Poliomyelitis is a highly infectious disease that, although not as prevalent as before, still haunts our planet and its people. The poliovirus is transmitted from person to person via primarily the fecal-oral route. The virus does not always translate to paralysis, fortunately. Only about 1% of infections were shown to lead to paralysis. [10] At one point, in the early 20th century, polio was one of the most dreaded diseases all around. Because it is a disease that attacks the central nervous system, many of those that are infected by it are left paralyzed. Children and those with weak immune systems are most vulnerable to polio but anyone can still contract the disease. Regardless of who it affected most, polio became an epidemic that was in dire need of eradication. Thus, in around the 1950s and 1960s, the polio vaccinations were introduced to the population, eliminating the major threat that polio had hung over the heads of everyone. In 1988, The Global Polio Eradication Initiative, a conglomeration of some of the biggest global health organizations like WHO, UNICEF, etc, was established to take immunizations against polio all around the world and kill the monstrous disease.[1]Due to this initiative, today, polio has almost disappeared from our planet, remaining in those few countries that consist of disadvantaged and closed off populations that are unable to keep all of their populations immunized and free of this menace.
Figure 1: The wild poliovirus seen through a microscope.
Target Information: This virus is generally defined as the inflammation of the gray matter of the spinal cord. It is of the family Picornaviridae. Polio is caused by the poliovirus, a human enterovirus that is a positive-strand RNA virus. It is made up of carbon, hydrogen, nitrogen, oxygen, phosphorus, and sulphur.[2] The virus includes an RNA genome that is enclosed in a protein shell called a capsid. There are three serotypes of the wild poliovirus that each embodies a different capsid protein although type 1 and type 3 are the two that tend to occasionally appear in the countries that have still not eliminated the disease. The genome of the virus is approximately 7430 bases in length and has a protein (VPg) linked covalently to the 5’ end that acts as primer during RNA synthesis for the poliovirus. [3] There are many studies still being done on the exact proteins involved in RNA genome replication of the poliovirus and when which is replicated at certain parts of the process of the poliovirus taking over. [5]
Figure 2: Poliovirus in the making. The figure shows the polyprotein of the virus and the process of it invading a cell.
The virus enters the body through the mouth, replicates in the throat and gastrointestinal tract and then moves into the bloodstream. [4] If the poliovirus has found shelter in the central nervous system and has begun to multiply, the spots of paralysis on the body could range from the legs to the brain. It annihilates the lower motor neurons that lead to loss of feeling and control for the muscles designated for swallowing, circulation, respiration, and the trunk, arms, and legs. Human nerve cells make it easier for the poliovirus to latch on because of their protruding protein structure on their surface. Although the functions of those protrusions are unknown, the poliovirus receptors attach to the virus and spread the disease through the cells, making thousands of copies of itself within hours. [2] The infection can be completely silent, have a minimal effect, or be deadly. In the case of the minor version of the disease called abortive poliomyelitis, there are simple symptoms like sore throat and a fever; however, with the major disease, paralysis and death are the drastic results. For the most part, the minor disease occurs within 7 days of infection while the major disease takes up to 30 days. [1]
Figure 4: A ribbon diagram of the capsid-binding of Pvr (poliovirus receptor). The viral segments are shown as tubes with VP1, blue; VP2, yellow; and VP3, red. Black balls are amino acids.
Drug Information: Two main types of polio vaccinations exist – the IPV or Inactivated Polio Vaccine and OPV or Oral Polio Vaccine. [1] In 1955, Dr. Jonas Salk developed IPV, which consists of inactivated poliovirus strains of all three poliovirus types. Its function is to produce antibodies in the blood of all the types of polio so that in the case of infection by the poliovirus, the antibodies can immediately react and block the spread of the virus to the central nervous system. IPV achieves its goal of protecting people from the virus, as it also carries no risk of vaccine-associated polio paralysis. However, it does induce low levels of immunity in the intestine, leaving the possibility of infection of the intestine feasible. Albert Sabin created the other vaccine, OPV, in 1961. It is also referred to as the trivalent oral polio vaccine or Sabin vaccine. [1] It is not like the usual vaccination because it is taken via drops in the mouth instead of being injected into the arm like the IPV is. It is made up of a mixture of live, but weakened poliovirus strains of all three types of the virus. It also produces antibodies of all three types of the virus to stop the spread of the virus if it enters the nervous system. In addition, OPV also produces a local, mucosal immune response in the mucous membrane of the intestines. [1] IPV is not able to limit the replication of the wild poliovirus inside the intestine like OPV can. This vaccination is administered orally and is relatively inexpensive in comparison to IPV. Although OPV is safe and effective, for several weeks after vaccination, the vaccine’s virus replicates in the intestine, is excreted in the feces and thus can be spread to others – especially in areas lacking hygiene and sanitation. A very rare but possible consequence of this form of the vaccine is that the virus may under go mutation and become circulating vaccine-derived polioviruses (cVDPV) or vaccine-associated paralytic polio (VAPP). [1]
Figure 4: The effect of polio vaccinations on the population over the period of 1950-2009.
Poliomyelitis is prevented by vaccination and is treatment with an assortment of medicines if contracted.
Motivation and Background:
Poliomyelitis is a highly infectious disease that, although not as prevalent as before, still haunts our planet and its people. The poliovirus is transmitted from person to person via primarily the fecal-oral route. The virus does not always translate to paralysis, fortunately. Only about 1% of infections were shown to lead to paralysis. [10] At one point, in the early 20th century, polio was one of the most dreaded diseases all around. Because it is a disease that attacks the central nervous system, many of those that are infected by it are left paralyzed. Children and those with weak immune systems are most vulnerable to polio but anyone can still contract the disease. Regardless of who it affected most, polio became an epidemic that was in dire need of eradication. Thus, in around the 1950s and 1960s, the polio vaccinations were introduced to the population, eliminating the major threat that polio had hung over the heads of everyone. In 1988, The Global Polio Eradication Initiative, a conglomeration of some of the biggest global health organizations like WHO, UNICEF, etc, was established to take immunizations against polio all around the world and kill the monstrous disease.[1]Due to this initiative, today, polio has almost disappeared from our planet, remaining in those few countries that consist of disadvantaged and closed off populations that are unable to keep all of their populations immunized and free of this menace.
Target Information:
This virus is generally defined as the inflammation of the gray matter of the spinal cord. It is of the family Picornaviridae. Polio is caused by the poliovirus, a human enterovirus that is a positive-strand RNA virus. It is made up of carbon, hydrogen, nitrogen, oxygen, phosphorus, and sulphur.[2] The virus includes an RNA genome that is enclosed in a protein shell called a capsid. There are three serotypes of the wild poliovirus that each embodies a different capsid protein although type 1 and type 3 are the two that tend to occasionally appear in the countries that have still not eliminated the disease. The genome of the virus is approximately 7430 bases in length and has a protein (VPg) linked covalently to the 5’ end that acts as primer during RNA synthesis for the poliovirus. [3] There are many studies still being done on the exact proteins involved in RNA genome replication of the poliovirus and when which is replicated at certain parts of the process of the poliovirus taking over. [5]
The virus enters the body through the mouth, replicates in the throat and gastrointestinal tract and then moves into the bloodstream. [4] If the poliovirus has found shelter in the central nervous system and has begun to multiply, the spots of paralysis on the body could range from the legs to the brain. It annihilates the lower motor neurons that lead to loss of feeling and control for the muscles designated for swallowing, circulation, respiration, and the trunk, arms, and legs. Human nerve cells make it easier for the poliovirus to latch on because of their protruding protein structure on their surface. Although the functions of those protrusions are unknown, the poliovirus receptors attach to the virus and spread the disease through the cells, making thousands of copies of itself within hours. [2] The infection can be completely silent, have a minimal effect, or be deadly. In the case of the minor version of the disease called abortive poliomyelitis, there are simple symptoms like sore throat and a fever; however, with the major disease, paralysis and death are the drastic results. For the most part, the minor disease occurs within 7 days of infection while the major disease takes up to 30 days. [1]
Drug Information:
Two main types of polio vaccinations exist – the IPV or Inactivated Polio Vaccine and OPV or Oral Polio Vaccine. [1] In 1955, Dr. Jonas Salk developed IPV, which consists of inactivated poliovirus strains of all three poliovirus types. Its function is to produce antibodies in the blood of all the types of polio so that in the case of infection by the poliovirus, the antibodies can immediately react and block the spread of the virus to the central nervous system. IPV achieves its goal of protecting people from the virus, as it also carries no risk of vaccine-associated polio paralysis. However, it does induce low levels of immunity in the intestine, leaving the possibility of infection of the intestine feasible. Albert Sabin created the other vaccine, OPV, in 1961. It is also referred to as the trivalent oral polio vaccine or Sabin vaccine. [1] It is not like the usual vaccination because it is taken via drops in the mouth instead of being injected into the arm like the IPV is. It is made up of a mixture of live, but weakened poliovirus strains of all three types of the virus. It also produces antibodies of all three types of the virus to stop the spread of the virus if it enters the nervous system. In addition, OPV also produces a local, mucosal immune response in the mucous membrane of the intestines. [1] IPV is not able to limit the replication of the wild poliovirus inside the intestine like OPV can. This vaccination is administered orally and is relatively inexpensive in comparison to IPV. Although OPV is safe and effective, for several weeks after vaccination, the vaccine’s virus replicates in the intestine, is excreted in the feces and thus can be spread to others – especially in areas lacking hygiene and sanitation. A very rare but possible consequence of this form of the vaccine is that the virus may under go mutation and become circulating vaccine-derived polioviruses (cVDPV) or vaccine-associated paralytic polio (VAPP). [1]
References:
1. The Global Polio Eradication Initiative. Polio Global Eradication Initiative. http://www.polioeradication.org/Home.aspx (accessed Feb 4, 2014).
2. Smithsonian National Museum of American History. Whatever Happened To Polio? http://amhistory.si.edu/polio/virusvaccine/livingchem.htm (accessed, Feb 1, 2014)
3. Minor, P. D., The polio-eradication programme and issues of the end game. J Gen Virol 2012, 93 (Pt 3), 457-74.
4. Nathanson, N.; Kew, O. M., From emergence to eradication: the epidemiology of poliomyelitis deconstructed. Am J Epidemiol 2010, 172 (11), 1213-29.
5. Cameron, C. E.; Oh, H. S.; Moustafa, I. M., Expanding knowledge of P3 proteins in the poliovirus lifecycle. Future Microbiol 2010, 5 (6), 867-81.
6. Grassly, N. C., The final stages of the global eradication of poliomyelitis. Philos Trans R Soc Lond B Biol Sci 2013, 368 (1623), 20120140.
7. PubMed Health. Poliomyelitis. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002375/#adam_001402.disease.treatment (accessed Feb 4, 2014).
8. U.S. National Institutes of Health. Clinicaltrials.gov.
http://clinicaltrials.gov/ct2/results?no_unk=Y&intr=Poliovirus+Vaccines (accessed, Feb 3, 2014)
9. World Health Organization. Poliomyelitis. http://www.who.int/biologicals/areas/vaccines/poliomyelitis/en/index.html (accessed, Jan 31, 2014)
10. Center for Disease Control. Poliomyelitis. http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/polio.pdf (accessed, Feb 18, 2014)
11. Minor, P. D., Polio eradication, cessation of vaccination and re-emergence of disease. Nature Reviews Microbiology 2004, 2, 473-482.